Younkin S G, Goodridge B, Katz J, Lockett G, Nafziger D, Usiak M F, Younkin L H
Fed Proc. 1986 Dec;45(13):2982-8.
In this study, we examined 26 cases of Alzheimer's disease (AD) and 14 age-matched controls. In Brodmann area 21 cerebral cortex of the AD cases, there was no change in soluble G1 and G4 acetylcholinesterase (AChE) (EC 3.1.1.7), a significant 40% decrease in membrane-associated G4 AChE, significant 342 and 406% increases in A12 and A8 AChE, and a significant 71% decrease in choline acetyltransferase (ChAT) (EC 2.3.1.6). Our working hypothesis to account for these changes postulates that soluble globular forms are unchanged because they are primarily associated with intrinsic cortical neurons that are relatively unaffected by AD, that ChAT and membrane-associated G4 AChE decrease because they are primarily associated with incoming axons of cholinergic neurons that are abnormal in AD, and that asymmetric forms of AChE increase because of an acrylamide-type impairment of fast axonal transport in diseased incoming cholinergic axons. In the nucleus basalis of Meynert (nbM) of the 26 AD cases, there was a significant 61% decrease in the number of cholinergic neurons, an insignificant 23% decrease in nbM ChAT, a significant 298% increase in nbM ChAT per cholinergic neuron, and a significant 7% increase in the area of cholinergic perikarya. To account for the increased ChAT in cholinergic neurons and the enlargement of cholinergic perikarya, we propose that slow axonal transport may be impaired in nbM cholinergic neurons in AD.
在本研究中，我们检查了26例阿尔茨海默病（AD）患者和14名年龄匹配的对照者。在AD患者的布罗德曼21区大脑皮质中，可溶性G1和G4乙酰胆碱酯酶（AChE）（EC 3.1.1.7）无变化，膜相关G4 AChE显著下降40%，A12和A8 AChE分别显著增加342%和406%，胆碱乙酰转移酶（ChAT）（EC 2.3.1.6）显著下降71%。我们对这些变化的工作假设是，可溶性球状形式未改变，因为它们主要与相对不受AD影响的内在皮质神经元相关；ChAT和膜相关G4 AChE下降，因为它们主要与AD中异常的胆碱能神经元传入轴突相关；AChE的不对称形式增加，是因为患病的胆碱能传入轴突中快速轴突运输受到丙烯酰胺型损伤。在26例AD患者的梅纳特基底核（nbM）中，胆碱能神经元数量显著减少61%，nbM ChAT无显著下降23%，每个胆碱能神经元的nbM ChAT显著增加298%，胆碱能核周体面积显著增加7%。为了解释胆碱能神经元中ChAT增加和胆碱能核周体增大的现象，我们提出AD中nbM胆碱能神经元的慢轴突运输可能受损。
